SUMMARY CORE C: CORRELATIVE SCIENCES Immuno-gene therapies have demonstrated an unparalleled anti-cancer efficacy in very poor prognosis patients. Limitations in the in vivo efficacy of the patient?s own T cells in CLL, antigen escape-related relapse in ALL, a CAR-engineered T cell pool outpaced by tumor cells in myeloma, and lack of appropriate, tumor- selective CAR in AML has given rise to the current proposal wherein innovative approaches are expected to solve the aforementioned challenges in cellular immunotherapy. Our trials will be the first to use CRISPR/Cas9-enhanced immune-gene therapy to treat some of the most challenging cases in each clinical indication; the first to use CART cells targeting two different antigens; the first to target AML with normal donor CART cells targeting CD33 while repopulating the host with CD33-edited hematopoietic stem cells. Critical to the success of cell therapies is a central correlative sciences laboratory to study the in vivo kinetics and homing of the infusion product(s) and the response of the tumor and the bioactivity of the infused cells; Core C provides this GCLP-based yet nimble infrastructure to support the clinical trials proposed herein, where SOP-specified molecular, cellular, and biochemical assays will be performed, reviewed by qualified personnel, and entered into a database for aggregate analysis to evaluate the efficacy of our proposed trials and compare with previously run CART cell trials at UPenn.